The ginkgo biloba extract (EGb 761) protects hippocampal neurons against cell death induced by beta-amyloid (original) (raw)
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European Journal of Neuroscience, 2000
Substantial evidence suggests that the accumulation of b-amyloid (Ab)-derived peptides, and to a lesser extent free radicals, may contribute to the aetiology and/or progression of Alzheimer's disease (AD). Ginkgo biloba extract (EGb 761) is a well-de®ned plant extract containing two major groups of constituents, i.e.¯avonoids and terpenoids. It is viewed as a polyvalent agent with a possible therapeutic use in the treatment of neurodegenerative diseases of multifactorial origin, e.g. AD. We have investigated here the potential effectiveness of EGb 761 against toxicity induced by (Ab)-derived peptides (Ab 25±35 , Ab 1±40 and Ab 1±42) on hippocampal primary cultured cells, this area being severely affected in AD. A co-treatment with EGb 761 concentration-dependently (10±100 mg/ mL) protected hippocampal neurons against toxicity induced by Ab fragments, with a maximal and complete protection at the highest concentration tested. Similar, albeit less potent protective effects were seen with the¯avonoid fraction of the extract (CP 205), while the terpenes were ineffective. Most interestingly, EGb 761 (100 mg/mL) was even able to protect (up to 8 h) hippocampal cells from a pre-exposure to Ab 25±35 and Ab 1±40. EGb 761 was also able to both protect and rescue hippocampal cells from toxicity induced by H 2 O 2 (50±150 mM), a major peroxide possibly involved in mediating Ab toxicity. Moreover, EGb 761 (10±100 mg/mL), and to a lesser extent CP 205 (10±50 mg/mL), completely blocked Ab-induced events, e.g. reactive oxygen species accumulation and apoptosis. These results suggest that the neuroprotective effects of EGb 761 are partly associated with its antioxidant properties and highlight its possible effectiveness in neurodegenerative diseases, e.g. AD via the inhibition of Ab-induced toxicity and cell death.
The effect of Ginkgo biloba extract on 3-nitropropionic acid-induced neurotoxicity in rats
Neurochemistry International, 2011
3-Nitropropionic acid (3-NP), an irreversible inhibitor of succinate dehydrogenase enzyme (SDH), induces neurodegeneration similar to that observed in Huntington’s disease (HD). Reduction of prepulse inhibition (PPI) of acoustic startle response, locomotor hypoactivity, bilateral striatal lesions as well as brain oxidative stress are major features of HD. The present study was designed to investigate neuroprotective effect of Ginkgo biloba extract (EGb 761) on 3-NP induced neurobehavioral changes and striatal lesions.Rats administered 3-NP (20 mg/kg, s.c.) for five consecutive days exhibited PPI deficits and locomotor hypoactivity whereas, pretreatment of animals with EGb 761 (100 mg/kg, i.p. for 15 days) ahead of and during the induction of HD by 3-NP (20 mg/kg for 5 days starting at day 8) ameliorated 3-NP-induced neurobehavioral deficits. Administration of 3-NP increased the level of striatal malondialdehyde (MDA). This effect was prevented in animals pre-treated with EGb 761. Changes in the level of apoptotic regulatory gene expressions, following 3-NP treatment, were demonstrated as both an up-regulation and a down-regulation of the expression levels of striatal Bax and Bcl-xl genes, respectively. In addition, an up-regulation of the expression level of striatal glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was also observed. Pre-treatment with EGb 761 caused a down-regulation in striatal GAPDH and Bax together with an up-regulation of striatal Bcl-xl expression level as compared to the 3-NP treated group. Histochemical examination of striatal tissue showed that EGb 761 significantly prevented 3-NP induced inhibition of SDH activity. Histopathological examination further affirmed the neuroprotective effect of EGb 761 against 3-NP toxicity.Taken together, these results suggest that EGb 761 has a neuroprotective role in the current HD paradigm, which may be related to improvement of energy metabolism, antioxidant properties and antiapoptotic effects.► 3-NP induces neurodegeneration similar to that observed in HD. ► EGb 761 benefits directed us to test its effects against 3-NP-induced HD. ► Results suggest that EGb 761 has a neuroprotective role against 3-NP-induced HD. ► EGb 761 protective mechanism attributed to antioxidant and antiapoptotic effects.
Neurological Research, 2009
The effects of ginsenosides were thought to prevent neurodegenerative processes associated with aging. The accumulation of b-amyloid protein (Ab) within the brain is one of the pathological hallmarks of Alzheimer's disease (AD). There is no one effective treatment of AD. To investigate the effects of ginsenoside Rb1 (GRb1) on neuronal damage induced by Ab and potential mechanisms of the effects of GRb1 in vitro, morphological observation and biochemical analysis combining primary cultured neurons were adopted. A positive control was pre-treated with Trolox. Neurons that were treated with Ab1-42 (2 mM) were shrunken perikaryon with loss of neurite processes; the survival rate of neurons decreased almost to 50% (p,0.01). Lactate dehydrogenase (LDH) release, malondialdehyde (MDA) product and superoxide dismutase (SOD) activity level all increased obviously (p,0.01 or p,0.05). However, neurons pre-treated with GRb1 (0.1, 1 and 10 mM) or Trolox (10 mM) had a survival rate increase compared with neurons treated with Ab alone; LDH release and MDA product decreased distinctly, and the increase in SOD activity in Ab-treated neurons was attenuated evidently (p,0.01 or p,0.05). Thus, we conclude that GRb1 exerted neuroprotection obviously. GRb1 protected neurons against the toxicity of Ab, most likely through an antioxidant pathway. GRb1 could be useful neuroprotective agents of AD. [Neurol Res 2009; 31: 663-667]
Research Journal of Pharmacognosy, 2020
Background and objectives: Alzheimer's disease (AD) is characterized by progressive cognitive decline. Oxidative stress plays a central role in the pathogenesis of AD. It has been proposed that administration of antioxidants affect cognitive processes, such as learning and memory. This study investigated the protective effects of vitamin E and Ginkgo biloba extract (as antioxidants) on learning and memory, hippocampal plasticity, and apoptotic marker proteins in a rat model of AD. Methods: The hyroalcoholic extract of Gingko biloba leaves wasprepared using maceration method. Male Wistar rats were randomly divided into six groups: control, sham received intra-hippocampal injection (I.H.P) of vehicle, AD model that received intra-hippocampal injection of the beta-amyloid (Aβ), AD+ vitamin E (200 mg/kg, i.p.), AD+ G. biloba (100 mg/kg/p.o.), and AD+ vitamin E (200 mg/kg, i.p.)+ G. biloba (100 mg/kg/p.o.). At the end of the treatments, the rats were subjected to the passive avoidanc...
Inhibition of amyloid- aggregation and caspase-3 activation by the Ginkgo biloba extract EGb761
Proceedings of the National Academy of Sciences, 2002
Standardized extract from the leaves of the Ginkgo biloba tree, labeled EGb761, has been used in clinical trials for its beneficial effects on brain functions, particularly in connection with agerelated dementias and Alzheimer's disease (AD). Substantial experimental evidence indicates that EGb761 protects against neuronal damage from a variety of insults, but its cellular and molecular mechanisms remain unknown. Using a neuroblastoma cell line stably expressing an AD-associated double mutation, we report that EGb761 inhibits formation of amyloid- (A) fibrils, which are the diagnostic, and possibly causative, feature of AD.
Journal of neuroinflammation, 2017
Ginkgo biloba has been reported to possess free radical-scavenging antioxidant activity and anti-inflammatory properties. In our pilot study, YY-1224, a terpene trilactone-strengthened extract of G. biloba, showed anti-inflammatory, neurotrophic, and antioxidant effects. We investigated the pharmacological potential of YY-1224 in β-amyloid (Aβ) (1-42)-induced memory impairment using cyclooxygenase-2 (COX-2) knockout (-/-) and APPswe/PS1dE9 transgenic (APP/PS1 Tg) mice. Repeated treatment with YY-1224 significantly attenuated Aβ (1-42)-induced memory impairment in COX-2 (+/+) mice, but not in COX-2 (-/-) mice. YY-1224 significantly attenuated Aβ (1-42)-induced upregulation of platelet-activating factor (PAF) receptor gene expression, reactive oxygen species, and pro-inflammatory factors. In addition, YY-1224 significantly inhibited Aβ (1-42)-induced downregulation of PAF-acetylhydrolase-1 (PAF-AH-1) and peroxisome proliferator-activated receptor γ (PPARγ) gene expression. These chang...
Nutrition, 2012
Ginkgo Biloba extract 761 (EGb 761) is a patented and well-defined mixture of active compounds extracted from Ginkgo biloba leaves. This extract contains two main groups of active compounds, flavonoids (24%) and terpenoids (6%). EGb 761 is used clinically to treat dementia and vasoocclusive and cochleovestibular disorders. This extract has neuroprotective effects, exerted probably by means of its antioxidant function. Parkinson's disease (PD) is a neurodegenerative disorder that affects 2% of the population older than 60 y. It produces a progressive loss of dopaminergic neurons and depletion of dopamine (DA), leading to movement impairment. The production of reactive oxygen species, which act as mediators of oxidative damage, is linked to PD. This disease is routinely treated with the DA precursor, L-3,4-dihydroxyphenylalanine. However, this produces severe side effects, and its neurotoxic properties can be due to a free radical production. Thus, administration of antioxidant drugs might be used to prevent neuronal death produced by oxidative mechanisms. The use of synthetic antioxidants has decreased because of their suspected activity as carcinogenic promoters. We describe the studies related to the antioxidant effect of EGb 761 in an animal model of PD. It has been shown that EGb761 can provide a neuroprotective/ neurorecovery effect against the damage to midbrain DA neurons in an animal model of PD. EGb 761 also has been found to lessen the impairment of locomotion, correlating with an increase of DA and other morphologic and biochemical parameters related to its antioxidant effect in an animal model of PD. These studies suggest it as an alternative in the future treatment of PD.
Background: Ginkgo biloba extract EGb761 has shown the neuroprotective effects on Alz-heimer's disease (AD) through the protection against the Aβ-induced neurotoxicity. However, it is not completedly clear whether EGb761 attenuates tau hyperphosphorylation, another of the most prominent mechanisms underlying the pathology of AD. Methods: we employed hyperhomocysteinemia (HHcy) to mimic AD like pathological alterations and memory deficits in rats as model, and injected EGb761 with or after HHcy injection as prevention and treatment, injected saline as control. We measured the status of oxidative damage and spatial and learning memory in rats. Then we detected the level of memory-related proteins, tau phosphorylation and the level and activity of tau kinase (GSK-3β) and phosphatase (PP2A) by Western blotting and Immunohis-tochemistry. Results: We found that EGb761 could significantly antagonize HHcy-induced oxidative damage, recover PP2Ac and GSK3β activities deregulated by HHcy. Furthermore, tau was hyperphosphorylated at Thr231, Ser262, Ser396, and Ser404, most common PP2Ac and GSK3β targeted sites in the hippocam-pus and prefrontal cortex of HHcy rats, whereas EGb761 recovered the tau phosphorylation at those sites. Behavioral tests revealed that EGb761 rescued HHcy-induced spatial reference memory deficit and upregulated the expression of synapse-associated protein PSD95 and synapsin-1. Conclusion: EGb761 might be a promising drug to treat AD through its anti-oxidative activity and decreasing tau hyperphosphorylation besides the protection against the Aβ-induced neurotoxicity.
2010
Background: Energy deficiency and mitochondrial failure have been recognized as a prominent, early event in Alzheimer's disease (AD). Recently, we demonstrated that chronic exposure to amyloid-beta (Ab) in human neuroblastoma cells overexpressing human wild-type amyloid precursor protein (APP) resulted in (i) activity changes of complexes III and IV of the oxidative phosphorylation system (OXPHOS) and in (ii) a drop of ATP levels which may finally instigate loss of synapses and neuronal cell death in AD. Therefore, the aim of the present study was to investigate whether standardized Ginkgo biloba extract LI 1370 (GBE) is able to rescue Ab-induced defects in energy metabolism.
The Journal of Neuroscience, 2006
Amyloid- (A) toxicity has been postulated to initiate synaptic loss and subsequent neuronal degeneration seen in Alzheimer's disease (AD). We previously demonstrated that the standardized Ginkgo biloba extract EGb 761, commonly used to enhance memory and by AD patients for dementia, inhibits A-induced apoptosis in neuroblastoma cells. In this study, we use EGb 761 and its single constituents to associate A species with A-induced pathological behaviors in a model organism, Caenorhabditis elegans. We report that EGb 761 and one of its components, ginkgolide A, alleviates A-induced pathological behaviors, including paralysis, and reduces chemotaxis behavior and 5-HT hypersensitivity in a transgenic C. elegans. We also show that EGb 761 inhibits A oligomerization and A deposits in the worms. Moreover, reducing oxidative stress is not the mechanism by which EGb 761 and ginkgolide A suppress A-induced paralysis because the antioxidant L-ascorbic acid reduced intracellular levels of hydrogen peroxide to the same extent as EGb 761, but was not nearly as effective in suppressing paralysis in the transgenic C. elegans. These findings suggest that (1) EGb 761 suppresses A-related pathological behaviors, (2) the protection against A toxicity by EGb 761 is mediated primarily by modulating A oligomeric species, and (3) ginkgolide A has therapeutic potential for prevention and treatment of AD.